The Association Between Pregnancy Timing and Cumulative Exposure on Survival in Melanoma.

BACKGROUND: As melanoma is common among young women, the impact of pregnancy on melanoma prognosis is of interest. OBJECTIVE: The purpose of this study was to examine the association between pregnancy and survival in female melanoma patients of childbearing age. METHODS: We performed a population-level, retrospective cohort study of women of childbearing age (18-45 years) diagnosed with melanoma from 2007 to 2017 using administrative data from Ontario, Canada. Patients were categorized according to pregnancy status (i.e. pregnancy before [conception from 60 to 13 months prior to melanoma], pregnancy-associated [conception 12 months prior to and after], and pregnancy after [conception 12 months after] melanoma). Cox models were used to examine melanoma-specific survival (MSS) and overall survival (OS) associated with pregnancy status. RESULTS: Of 1312 women with melanoma, most did not experience pregnancy (84.1%), with 7.6% experiencing a pregnancy-associated melanoma and 8.2% experiencing a pregnancy after melanoma. Pregnancy before melanoma occurred in 18.1% of patients. Pregnancy before (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.35-1.28), associated (HR 1.15, 95% CI 0.45-2.97), and after melanoma (HR 0.39, 95% CI 0.13-1.11) was not associated with a difference in MSS compared with those who did not experience a pregnancy during these time periods. Pregnancy status was also not associated with a difference in OS (p > 0.05). Cumulative weeks pregnant were not associated with a difference in MSS (4-week HR 0.99, 95% CI 0.92-1.07) or OS (4-week HR 1.00, 95% CI 0.94-1.06). CONCLUSIONS: In this population-level analysis of female melanoma patients of childbearing age, pregnancy was not associated with a difference in survival, suggesting that pregnancy is not associated with a worse melanoma prognosis.

Sarcopenia and frailty as predictors of surgical morbidity and oncologic outcomes in retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPS) are rare tumors for which surgical resection is the principal treatment. There is no established model to predict perioperative risks for RPS. We evaluated the association between preoperative sarcopenia, frailty, and hypoalbuminemia with surgical and oncological outcomes. METHODS: We performed a prospective cohort analysis of 65 RPS patients who underwent surgical resection. Sarcopenia was defined as Total Psoas Area Index ≤ 1st quintile by sex. Frailty was estimated using the modified frailty index (mFI). Logistic regression models were used to assess predictors of 30-day postoperative morbidity. The Kaplan-Meier method with log-rank test was utilized to assess factors associated with overall (OS) and recurrence-free survival (RFS). RESULT: Sarcopenia was associated with worse OS with a median of 54 compared with 158 months (p = 0.04), but no differences in RFS (p > 0.05). Hypoalbuminemia was associated with worse OS with a median of 72 compared with 158 months (p < 0.01). MFI scores were not associated with OS or RFS (p > 0.05). Sarcopenia, mFI, and hypoalbuminemia were not associated with postoperative morbidity (p > 0.05). CONCLUSION: This study suggests that sarcopenia may be utilized as a measure of overall fitness, rather than a cancer-specific risk, and the mFI is a poor predictive measure of outcomes in RPS.

Disparities in treatment and survival in early-stage hepatocellular carcinoma in California.

BACKGROUND AND OBJECTIVES: Curative intent therapy is the standard of care for early-stage hepatocellular carcinoma (HCC). However, these therapies are under-utilized, with several treatment and survival disparities. We sought to demonstrate whether the type of facility and distance from treatment center (with transplant capabilities) contributed to disparities in curative-intent treatment and survival for early-stage HCC in California. METHODS: We performed a retrospective analysis of the California Cancer Registry for patients diagnosed with stage I or II primary HCC between 2005 and 2017. Primary and secondary outcomes were receipt of treatment and overall survival, respectively. Multivariable logistic regression and Multivariable Cox proportional hazards regression were used to evaluate associations. RESULTS: Of 19 059 patients with early-stage HCC, only 36% (6778) received curative-intent treatment. Compared to Non-Hispanic White patients, Hispanic patients were less likely, and Asian/Pacific Islander patients were more likely to receive curative-intent treatment. Our results showed that rural residence, public insurance, lower neighborhood SES, and care at non-National Cancer Institute-designated cancer center were associated with not receiving treatment and decreased survival. CONCLUSIONS: Although multiple factors influence receipt of treatment for early-HCC, our findings suggest that early intervention programs should target travel barriers and access to specialist care to help improve oncologic outcomes.

Chemotherapy After Diagnosis of Malignant Bowel Obstruction is Associated with Superior Survival for Medicare Patients with Advanced Malignancy.

BACKGROUND: Although malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival. METHODS: This retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival. RESULTS: Of the 2983 MBO patients, 39% (n = 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard ratio [SHR], 0.96; 95% confidence interval [CI], 0.86-1.07; p = 0.47) or multivariable analysis (SHR, 1.12; 95% CI, 1.00-1.26; p = 0.06). Older age, African American race, medical comorbidities, non-colorectal and non-ovarian cancer diagnoses, sepsis, ascites, and intensive care unit stays were inversely associated with receipt of chemotherapy after MBO (p < 0.05). Chemotherapy with surgery was associated with longer survival than surgery (adjusted hazard ratio [aHR], 2.97; 95% CI, 2.65-3.34; p < 0.01) or medical management without chemotherapy (aHR, 4.56; 95% CI, 4.04-5.14; p < 0.01). Subgroup analyses of biologically diverse cancers (colorectal, pancreatic, and ovarian) showed similar results, with greater survival related to chemotherapy (p < 0.05). CONCLUSIONS: Chemotherapy plays an integral role in maximizing oncologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.

The Role of Radiation Therapy in Addition to Lumpectomy and Hormone Therapy in Men 70 Years of Age and Older with Early Breast Cancer: A NCDB Analysis.

PURPOSE: Current treatment guidelines for male breast cancer are guided by female-only trials despite data suggesting distinct clinicopathologic differences between sexes. We sought to evaluate whether radiation therapy (RT) after lumpectomy was associated with equivalent survival among men > 70 years of age with stage I, estrogen receptor (ER) positive tumors, as seen in women from the Cancer and Leukemia Group B (CALGB) 9343 trial. METHODS: We performed a retrospective analysis of 752 stage I, ER-positive male breast cancer patients ≥ 70 years who were treated with hormone therapy and surgery, with or without RT, from the National Cancer Database between 2004 and 2014. Patients were categorized based on surgery and RT (lumpectomy alone, lumpectomy with RT, and mastectomy alone). Multivariable Cox proportional hazards regression analysis was used to compare overall survival between treatment groups. RESULTS: Most patients underwent total mastectomy, with only 32.6% treated with lumpectomy. Of those who underwent lumpectomy, 72.7% received adjuvant RT. In multivariate analysis, there was no statistical difference in overall survival when comparing lumpectomy alone and lumpectomy with RT (aHR 0.72 [95% CI 0.38-1.37], p = 0.31) or when comparing lumpectomy (alone or with RT) and mastectomy (aHR 1.28 [95% CI 0.88-1.87], p = 0.20). CONCLUSIONS: In this national sample of elderly men with ER-positive early-stage disease treated with endocrine therapy, there were no significant differences in overall survival when comparing lumpectomy alone and lumpectomy with RT, or lumpectomy (alone or with RT) and mastectomy. These results suggest that less aggressive treatment may be appropriate for a subset of male breast cancer patients.

Is Breast-Conserving Therapy Appropriate for Male Breast Cancer Patients? A National Cancer Database Analysis.

BACKGROUND: Current treatment guidelines for male breast cancer are predominantly guided by female-only clinical trials. With scarce research, it is unclear whether breast-conserving therapy (BCT) is equivalent to mastectomy in men. We sought to compare overall survival (OS) among male breast cancer patients who underwent BCT versus mastectomy. METHODS: We performed a retrospective analysis of 8445 stage I-II (T1-2 N0-1 M0) male breast cancer patients from the National Cancer Database (2004-2014). Patients were grouped according to surgical and radiation therapy (RT). BCT was defined as partial mastectomy followed by RT. Multivariable and inverse probability of treatment-weighted (IPTW) Cox proportional hazards models were used to compare OS between treatment groups, controlling for demographic and clinicopathologic characteristics. RESULTS: Most patients underwent total mastectomy (61.2%), whereas 18.2% underwent BCT, 12.4% underwent total mastectomy with RT, and 8.2% underwent partial mastectomy alone. In multivariable and IPTW models, partial mastectomy alone, total mastectomy alone, and total mastectomy with RT were associated with worse OS compared with BCT (p < 0.001 all). Ten-year OS was 73.8% for BCT and 56.3, 58.0 and 56.3% for other treatment approaches. Older age, higher T/N stage, histological grade, and triple-negative receptor status were associated with poorer OS (p < 0.05). Subgroup analysis by stage demonstrated similar results. CONCLUSIONS: In this national sample of male breast cancer patients, BCT was associated with greater survival. The underlying mechanisms of this association warrant further study, because more routine adoption of BCT in male breast cancer appears to translate into clinically meaningful improvements in survival.

Interhospital Variability in Quality Outcomes of Pancreatic Surgery.

BACKGROUND: Assessment of optimal patient outcomes from health care delivery is critical for success amidst current reform. We developed a composite index of quality for pancreaticoduodenectomy (PD) and compared high and low performers nationwide. METHODS: We performed a retrospective analysis of 17,220 patients undergoing elective PD between October 2010 and June 2014 using the Vizient database. A quality index score (QIS) was developed from five variables associated with optimal outcomes: postoperative complication rate, length of stay, 30-d readmission rate, mortality rate, and hospital volume. Value was defined as hospital-based QIS divided by mean hospital charges. High-value centers (top quintile) were compared to low-value centers (bottom quintile). RESULTS: The majority of high-value centers (79%) achieved top performer status in 1-2 of five quality categories though only 11% were low performer in at least one category. Conversely, 41% of low-value centers were top performers in at least one category, although rarely more than one (8%); 63% of low-value centers were low performers in two or more categories. There was no significant association between QIS and hospital charges (-570, 95% CI -1308 to 168, P = 0.13). CONCLUSIONS: High-value centers infrequently provided high quality surgical care across all five metrics but instead excelled in a few quality metrics while avoiding low performance in any quality metric. Although low-value centers could achieve excellence in one quality metric, they were frequently low performers in two or more outcomes. Improvements in value of PD can be achieved by a consistent effort across all quality metrics rather than efforts at constraining financial expenditures of health care delivery.

Clinical Outcomes and Costs Following Unplanned Excisions of Soft Tissue Sarcomas in the Elderly.

BACKGROUND: Surgical guidelines for soft tissue sarcoma (STS) emphasize pretreatment evaluation and reports of the perils of unplanned excision exist. Given the paucity of population-based data on this topic, our objective was to analyze clinical outcomes and costs of planned versus unplanned STS excisions in the Medicare population. METHODS: We analyzed 3913 surgical patients with STS ≥66 y old from 1992 to 2011 using the Surveillance, Epidemiology, and End Results-Medicare datafiles. Planned excisions were classified based on preoperative MRI and/or biopsy, whereas unplanned excisions were classified by excision as the first procedure. Inverse probability of treatment weighting with propensity scores was used to adjust for clinicopathologic differences. Re-excisions, complications, and Medicare payments were compared with multivariate models. Overall survival and disease-specific survival were analyzed using Cox proportional hazards and competing risk models. RESULTS: Before the first excision, 24.3% had an MRI and biopsy, 27.3% had an MRI, 11.4% had a biopsy, and 36.9% were unplanned. Re-excision rates were highest for unplanned excisions: 46.3% compared to 18.1%, 36.4%, and 29.7% for other groups (P < 0.0001). There was no difference in disease-specific survival or overall survival between groups (P > 0.05). Planned excisions were associated with increased Medicare costs (P < 0.05), with the first resection contributing to the majority of costs. Subgroup analyses by histologic grade and tumor size revealed similar results. CONCLUSIONS: Survival was comparable with greater health care costs in elderly patients undergoing planned STS excision. Although unplanned excisions remain a quality of care issue with high re-excision rates, these data have important implications for the surgical management of STS in the elderly.

Extremity soft tissue sarcoma in the elderly: Are we overtreating or undertreating this potentially vulnerable patient population?

BACKGROUND: As the U.S. population ages, differences in oncologic outcomes among the elderly have been recognized. Our objective was to analyze the clinical, pathologic, and treatment outcomes for elderly soft tissue sarcoma (STS) patients, hypothesizing significant differences in the management and response to therapy. METHODS: Using the National Cancer Database, we identified 33 859 patients with nonmetastatic extremity STS. We defined elderly as ≥74 years in age and compared patient and treatment variables between adult and elderly patients. Cox-proportional hazards analysis was used to determine predictors of overall survival (OS). RESULTS: We identified 8504 elderly patients. Significant differences in histologic subtype, grade, and facility type between elderly and nonelderly patients (P < 0.05) exist. Elderly patients were less likely to undergo R0 resection (P = 0.001) and had a higher 90-day mortality (P = 0.001). Surgical elderly patients experienced superior OS compared with nonsurgical patients (P = 0.001). Among elderly patients, younger age, and female sex, lower Charlson-Deyo score, lower grade, smaller tumors, surgical resection, negative surgical margins, and radiation therapy were associated with better OS. CONCLUSIONS: Key differences exist in elderly extremity STS patients, including a narrower benefit/risk ratio with surgical management. These data highlight that elderly patients represent a distinct cohort for whom more careful selection appears indicated.

Drivers of Cost for Pancreatic Surgery: It's Not About Hospital Volume.

BACKGROUND: Outcomes for pancreatic resection have been studied extensively due to the high morbidity and mortality rates, with high-volume centers achieving superior outcomes. Ongoing investigations include healthcare costs, given the national focus on reducing expenditures. Therefore, we sought to evaluate the relationships between pancreatic surgery costs with perioperative outcomes and volume status. METHODS: We performed a retrospective analysis of 27,653 patients who underwent elective pancreatic resections from October 2013 to June 2017 using the Vizient database. Costs were calculated from charges using cost-charge ratios and adjusted for geographic variation. Generalized linear modeling adjusting for demographic, clinical, and operation characteristics was performed to assess the relationships between cost and length of stay, complications, in-hospital mortality, readmissions, and hospital volume. High-volume centers were defined as hospitals performing ≥ 19 operations annually. RESULTS: The unadjusted mean cost for pancreatic resection and corresponding hospitalization was $20,352. There were no differences in mean costs for pancreatectomies performed at high- and low-volume centers [- $1175, 95% confidence interval (CI) - $3254 to $904, p = 0.27]. In subgroup analysis comparing adjusted mean costs at high- and low-volume centers, there was no difference among patients without an adverse outcome (- $99, 95% CI - $1612 to 1414, p = 0.90), one or more adverse outcomes (- $1586, 95% CI - $4771 to 1599, p = 0.33), or one or more complications (- $2835, 95% CI - $7588 to 1919, p = 0.24). CONCLUSIONS: While high-volume hospitals have fewer adverse outcomes, there is no relationship between surgical volume and costs, which suggests that, in itself, surgical volume is not an indicator of improved healthcare efficiency reflected by lower costs. Patient referral to high-volume centers may not reduce overall healthcare expenditures for pancreatic operations.

Hospital utilization and disposition among patients with malignant bowel obstruction: a population-based comparison of surgical to medical management.

BACKGROUND: Malignant bowel obstruction (MBO) is often a terminal event in end-stage cancer patients. The decision to intervene surgically is complex, given the risk of harm in patients with a limited lifespan. Therefore, we sought to compare clinically meaningful outcomes in MBO patients treated with surgical versus medical management using population-based data. METHODS: We performed a retrospective analysis of hospitalized patients with MBO from 2006 to 2010 using the California Office of Statewide Health Planning and Development dataset. Hospital-free days (HFDs) at 30-, 90-, and 180-days were calculated accounting for all hospitalization, emergency department visit, and skilled nursing facility lengths of stay. Adjusted regression models were used to compare HFDs, disposition, complications, in-hospital death, and survival for surgical versus medical MBO cohorts, using inverse probability of treatment weighting with propensity scores. RESULTS: Of 4576 MBO patients, 3421 (74.8%) were treated medically and 1155 (25.2%) were treated surgically. Surgical patients had higher rates of complications (44.0% vs. 21.3%, p < 0.0001) and in-hospital death (9.5% vs. 3.9%, p < 0.0001) with lower rates of disposition to home (76.3% vs. 89.8%, p < 0.0001). Surgical patients had fewer 30- and 90-day HFDs compared to medical patients (p < 0.01). However, at 180-days, there were no differences in HFDs between treatment groups. There was no difference in overall survival between surgical and medical patients (median 6.5 vs. 6.4 months). CONCLUSION: In this population-based analysis, medical management was associated with less hospital utilization at 30- and 90-days, fewer in-hospital deaths, and more frequent discharges to home. These data underscore the potential benefits of medical management for MBO patients at the end-of-life.

Comparison of common risk stratification indices to predict outcomes among stage IV cancer patients with bowel obstruction undergoing surgery.

BACKGROUND AND OBJECTIVES: Among patients with disseminated malignancy (DMa), bowel obstruction is common with high operative morbidity. Since preoperative risk stratification is critical, we sought to compare three standard risk indices, the American Society of Anesthesiology (ASA) classification, Charlson comorbidity index (CCI), and modified frailty index (mFI). METHODS: We identified 1928 DMa patients with bowel obstruction who underwent an abdominal operation from 2007 to 2012 American College of Surgeons National Surgical Quality Improvement Program. Multivariate analyses assessed predictors of prolonged length of stay (LOS), 30-day serious morbidity and mortality. Receiver operating characteristics' areas under the curves (AUCs) for risk indices scores and 30-day mortality were assessed. RESULTS: Serious morbidity and mortality rates were 20.4% and 14.8%. ASA and CCI did not predict serious morbidity or prolonged LOS, but were predictors of mortality. The mFI did not predict prolonged LOS, but did predict serious morbidity and mortality. Subgroup analyses showed similar results. There were no significant differences between ASA, CCI, and mFI AUCs for mortality. CONCLUSIONS: ASA, CCI, and mFI are limited in their ability to predict postoperative adverse events among DMa patients undergoing surgery for bowel obstruction. These data suggest that a more tailored preoperative risk stratification tool would improve treatment planning.

Neoadjuvant Radiotherapy is Associated with R0 Resection and Improved Survival for Patients with Extremity Soft Tissue Sarcoma Undergoing Surgery: A National Cancer Database Analysis.

BACKGROUND: Neoadjuvant radiotherapy (RT) is increasingly advocated for the management of soft tissue sarcoma (STS). Therefore, this study sought to characterize the impact of neoadjuvant RT on rates of R0 resection and overall survival (OS) in extremity STS patients undergoing surgery. METHODS: From January 2003 to December 2012, the study identified patients with a diagnosis of extremity STS from the National Cancer Database. After exclusion of patients younger than 18 years, not treated by surgery, who had metastases at diagnosis, intraoperative RT, and missing or unknown data, 27,969 patients were identified. Logistic regression and Cox-proportional hazard analysis were used to compare rates of R0 resection among preoperative, postoperative, and no-RT cohorts and to determine predictors of R0 resection and OS. RESULTS: The mean age of the patients was 59.5 ± 17.1 years, and 45.9% were female. The median tumor size was 10.5 cm. The data showed that 51% of the patients did not receive RT, 11.8% received preoperative RT, and 37.2% received postoperative RT. The rates of R0 resection were 90.1% for the preoperative RT cohort, 74.9% for the postoperative RT cohort, and 79.9% for the no-RT cohort (P < 0.001). The independent predictors for achievement of R0 resection included academic facility type (odds ratio [OR] 1.36; 95% confidence interval [CI] 1.20-1.55), histologic subtype, tumor size (OR 0.99; 95% CI 0.99-0.99), Charlson score (OR 0.92; 95% CI 0.84-0.99), and preoperative RT (OR 1.83; 95% CI 1.61-2.07). Both R0 resection and RT (pre- or post-operative) were associated with increased OS. CONCLUSIONS: Preoperative RT independently predicts higher rates of R0 resection for patients with extremity STS undergoing surgical resection. Negative surgical margins and pre- or postoperative RT are associated with improved OS.

The modified frailty index to predict morbidity and mortality for retroperitoneal sarcoma resections.

BACKGROUND: The modified frailty index (mFI) is an important method to risk-stratify surgical patients and has been validated for general surgery and selected surgical subspecialties. However, there are currently no data assessing the efficacy of the mFI to predict acute morbidity and mortality in patients undergoing surgery for retroperitoneal sarcoma. METHODS: Using the American College of Surgeons' National Surgical Quality Improvement Program from 2007 to 2012, we performed a retrospective analysis of patients with a diagnosis of primary malignant retroperitoneal neoplasm who underwent surgical resection. The mFI was calculated according to standard published methods. Univariate and multivariate statistical analyses including χ2 and logistic regression were used to identify predictors of 30-d overall morbidity, 30-d severe morbidity (Clavien III/IV), and 30-d mortality. RESULTS: We identified 846 patients with the diagnosis of primary malignant retroperitoneal neoplasm who underwent surgical resection. The distribution mFI scores was 0 (48.5%) or 1 (36.3%), with only 4.5% of patients presenting with a score ≥3. Rates of 30-d overall morbidity, serious morbidity, and mortality were 22.6%, 12.9%, and 1.2%, respectively. Only selected mFI scores were associated with serious morbidity and overall morbidity on multivariate analysis (P < 0.05), and mFI did not predict 30-d mortality (P > 0.05). CONCLUSIONS: Our data demonstrate that the majority of patients undergoing retroperitoneal sarcoma resections have few, if any, comorbidities. The mFI was a limited predictor of overall and serious complications and was not a significant predictor of mortality. Better discriminators of preoperative risk stratification may be needed for this patient population.

Current perioperative outcomes for patients with disseminated cancer.

BACKGROUND: Surgical morbidity and mortality (M&M) for patients with disseminated malignancy (DMa) is high, and some have questioned the role of surgery. Therefore, we sought to characterize temporal trends in M&M among DMa patients, hypothesizing that surgical intervention would remain prevalent. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program from 2006-2010. Excluding patients undergoing a primary hepatic operation, we identified 21,755 patients with DMa. Parametric and/or nonparametric statistics and logistic regression were used to evaluate temporal trends and predictors of M&M. RESULTS: The prevalence of surgical intervention for DMa declined slightly over the time period, from 1.9%-1.6% of all procedures (P < 0.01). Among DMa patients, the most frequent operations performed were bowel resection, other gastrointestinal procedures, and multivisceral resections, these all showed small statistically significant decreases over time (P < 0.01). The rate of emergency operations also decreased (P < 0.01). In contrast, the rate of preoperative independent functional status rose, whereas the rate of preoperative weight loss and sepsis decreased (P < 0.01). Rates of 30-d morbidity (33.7 versus 26.6%), serious morbidity (19.8 versus 14.2%), and mortality (10.4 versus 9.3%) all decreased over the study period (P < 0.05). Multivariate analysis identified standard predictors (e.g., impaired functional status, preoperative weight loss, preoperative sepsis, and hypoalbuminemia) of worse 30-d M&M. CONCLUSIONS: Thirty-day morbidity, serious morbidity, and mortality have decreased incrementally for patients with DMa undergoing surgical intervention, but surgical intervention remains prevalent. These data further highlight the importance of careful patient selection and goal-directed therapy in patients with incurable malignancy.

Second primary cancers and survival among neuroendocrine tumor patients.

There is an increased risk of second primary cancers (SPCs) after neuroendocrine tumor (NET) diagnosis. The clinical significance of SPCs in this population is unknown. The purpose of this study was to evaluate the association between SPCs after NET diagnosis and survival. We performed a population-based, retrospective cohort study of NET patients (gastrointestinal, pancreatic, or lung primary) from 2000 to 2016 using the Surveillance, Epidemiology, and End Results database. Cox regression models assessed the association between SPCs and NET-specific (NET-SS), cancer-specific (CSS), and overall survival (OS). Of 58,553 NET patients, 7.9% experienced an SPC. SPCs were associated with worse OS (hazard ratio (HR) 2.14, 95% CI 1.94-2.36) and CSS (HR 2.31, 95% CI 2.06-2.59) with no difference in NET-SS (HR 1.04, 95% CI 0.87-1.23). Stratified analyses by histologic grade showed similar results for well and moderately differentiated NETs, but no difference in OS or CSS for poorly differentiated NETs (P > 0.05). In stratified analyses by NET site, SPCs were associated with worse OS (HR 3.41, 95% CI 3.01-3.87) and CSS (HR 4.96, 95% CI 4.28-5.74) in gastrointestinal NETs and worse OS (HR 1.25, 95% CI 1.03-1.52) with no difference in CSS (HR 1.08, 95% CI 0.85-1.36) in lung NETs. SPCs were not associated with a difference in OS or CSS in pancreatic NETs (P > 0.05). In conclusion, SPCs after NETs were associated with inferior OS and CSS compared to no SPC but were not associated with NET-SS. These data highlight the need for long-term follow-up in NETs to include the detection of SPCs to ensure early diagnosis and timely management.